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Corticosteroid injections may not always be the best solution for all arthritis patients. Gordon Schirmer/EyeEm/Stocksy
  • Two independent studies investigated the effect of pain-relieving corticosteroid and hyaluronic acid knee joint injections on the progression of knee osteoarthritis.
  • Both studies found that corticosteroid knee injections were associated with increased progression of knee osteoarthritis compared to controls and to hyaluronic acid injections.
  • These findings imply that corticosteroid knee injections must be administered with caution and that hyaluronic acid injections may be safer.

Osteoarthritis is a condition that develops when the protective cartilage in joints wears down, causing the bones to rub against each other. This condition frequently affects the knee. Typical symptoms of knee osteoarthritis are pain during physical activity, restricted mobility, stiffness, soreness, swelling around the knee, feeling like the joint may “give out,” and deformities such as knock knees or bowlegs.

Knee osteoarthritis is estimated to affect around 1 in 5 American adults ages 45 years and older. People who are over the age of 50, overweight, have a family history of knee osteoarthritis, or have experienced other knee problems are more likely to develop knee osteoarthritis.

Each year, more than 10% of patients with knee osteoarthritis receive joint injections to manage their symptoms. Corticosteroid injections provide short-term (4 to 8 weeks) pain relief, whereas more expensive hyaluronic acid injections alleviate knee osteoarthritis symptoms for longer periods.

In recent years, concerns have been raised regarding the safety of corticosteroid knee injections.

In 2017, a randomized clinical trial found that repeated corticosteroid injections had no greater pain-relieving effect than saline injections after 2 years but were associated with greater osteoarthritis progression.

Now, two new independently conducted studies provide further evidence that corticosteroid knee injections may accelerate the progression of knee osteoarthritis.

One study—led by Dr. Upasana Bharadwaj from the University of California, San Francisco (UCSF)—looked at the association between the type of knee injection (corticosteroid or hyaluronic acid) and progression of knee osteoarthritis using whole-organ magnetic resonance imaging scores (WORMS) over a period of 4 years.

The second study—led by Azad Darbandi from the Chicago Medical School of Rosalind Franklin University of Medicine and Science—looked at the progression of knee osteoarthritis in patients who received corticosteroid and hyaluronic acid injections using X-ray imaging analysis over a period of 4 years.

The results of both studies were presented on November 29, 2022, at the annual meeting of the Radiological Society of North America (RSNA).

Both studies used data from the Osteoarthritis Initiative (OAI)—a multi-center, observational study of individuals with knee osteoarthritis, currently in its 14th year of follow-up, sponsored by the National Institutes of Health.

The 1st study

Dr. Bharadwaj’s team at UCSF selected 70 patients from the OAI cohort who received a single injection, at a single timepoint, of either corticosteroid (n=44) or hyaluronic acid (n=26), and for whom MRI data was available at 2 years pre-injection, at the time of injection and at 2 years post-injection.

As a control group, the researchers selected 140 participants who did not receive injections during a two-year period and who were matched to the treatment group by age, sex, body mass index, pain and physical activity scores, and severity of disease.

Dr. Bharadwaj and her coworkers analyzed the patients’ MRI data, which enabled a detailed assessment of the whole knee joint (including the cartilage, meniscus, and bone marrow), as well as the accumulation of fluid in the intra-articular space. They assessed osteoarthritis progression by comparing the initial MRI scans to the MRI scans at 2 years post-injection.

The researchers found that patients who received corticosteroid knee injections had increased progression of knee osteoarthritis compared to controls and participants who received hyaluronic acid. Hyaluronic acid knee injections were associated with significantly lower progression of knee osteoarthritis, specifically in bone marrow lesions, compared to controls.

When asked about the study’s limitations and next steps, Dr. Thomas M. Link, study co-author and professor of radiology at UCSF School of Medicine, told Medical News Today:

“This is observational data from the Osteoarthritis Initiative cohort and not a controlled trial. A controlled trial with rigorous inclusion/exclusion criteria and study design would be the next step.”

The 2nd study

In the second study, researchers at the Chicago Medical School selected 150 patients from the OAI cohort who had similar baseline characteristics and who received either corticosteroid injections (n=50), hyaluronic acid injections (n=50), or who were not injected over a 3-year period (n=50).

Unlike the UCSF study, which used MRI data, the Chicago Medical School study used X-ray imaging. The researchers compared X-ray images of the knee at baseline and 4 years after. The treatment lasted 3 years.

They found that, in comparison to patients who received hyaluronic acid injections or no injections, patients injected with corticosteroids had significantly higher osteoarthritis progression, characterized by medial joint space narrowing.

“These two recent studies, using advanced imaging methods to detect joint health changes, add to the growing evidence that the risks of harm [from injected corticosteroids] are real and not insignificant,” said Dr. J. Haxby Abbott, professor at the University of Otago, New Zealand, specializing in musculoskeletal clinical epidemiology and the management of osteoarthritis, speaking to MNT.

“These findings should reinforce the guideline recommendations that these injections be reserved for only a small proportion of patients, after safer more effective treatments have not proven sufficiently effective, and should give physicians pause to consider how strongly indicated joint injection is, to help inform the choice of therapy that is most appropriate for each patient’s circumstances.”
— Dr. J. Haxby Abbott

Dr. Ewa M. Roos, professor of physiotherapy and head of the research at the research unit for musculoskeletal function and physiotherapy at the University of Southern Denmark, told MNT that the current guidelines “recommend patient education, exercise therapy, and weight loss, if needed, as core treatment for [osteoarthritis].”

Dr. Roos said that while hyaluronic acid injection may have a greater pain-relieving effect than a placebo, “all patients should have had a serious try of core treatment for at least 3-6 months first. For many, the pain relief is considerable, and for all, physical function improve after exercise.”

“Improved physical activity is not seen after other treatments only targeting pain such as pharmacological pain relievers, injections or surgery. This is important since many people with [osteoarthritis] have a very low physical activity level, and improvement will positively affect not only their independence but also their general health,” she added.

Dr. Abbott echoed Dr. Roos’ comments in favor of exercise therapy, patient education, and weight management as first-line treatments.

“Over the past decade, guidelines across the world have gradually retreated from recommending both oral and injected therapies due to more evidence coming out regarding the potential harms, especially of prolonged medication use,” he said.

When to try corticosteroids

“In cases where the core first-line interventions have not sufficiently improved pain and function, use of first topical and then oral nonsteroidal anti-inflammatory drugs (NSAIDs) is indicated, at the lowest effective dose and limited to the shortest time needed. Should these, too, not be sufficiently effective, or to control breakthrough pain flares, physicians may turn to injected corticosteroids.”
— Dr. J. Haxby Abbott